Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 5, 2012
Publication Date: March 15, 2012
Citation: Nelson, C.D., Reinhardt, T.A., Lippolis, J.D., Sacco, R.E., Nonnecke, B.J. 2012. Vitamin D signaling in the bovine immune system: A model for understanding human vitamin D requirements. Nutrients. 4(3):181-196. Interpretive Summary: Cattle offer a valuable model for understanding vitamin D requirements for optimal health in humans. Cattle, like humans, rely on synthesis of vitamin D3 in their skin for acquisition of vitamin D, and the physiological effects of vitamin D are quite similar between cattle and humans. Recent observations indicate that the vitamin D pathway influences broad aspects of immune function in cattle as it does in humans. Research examining the effects of vitamin D on the severity of experimentally induced mastitis in dairy cattle has provided evidence for a vitamin D signaling pathway in macrophages, and has demonstrated the potential for vitamin D to reduce the severity of experimentally induced bovine mastitis. Preliminary research also suggests that experimentally induced alterations in the vitamin D status of the preruminant calf influence gene and protein expression associated with the adaptive (i.e., antigen-specific) immune response as well as the response of the calf to aerosol challenge with respiratory syncytial virus, a significant cause of respiratory disease in young calves. Taken together, these studies indicate that the bovine model offers a valuable approach for investigating the influence of vitamin D on immune system and infectious disease response, thus providing insight into the role of vitamin D in promoting health in humans as well as cattle.
Technical Abstract: The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance.